Capillary fragility is a very common problem, in particular among the female population. The intake of anticoagulant drugs, infections, deficiency of certain vitamins and heredity can result in decreased capillary resistance.
The therapeutic use of aminaphtone (2-hydroxy-3-methyl-4-naphthohydroquinone-2-p-aminobenzoate) as vasoprotective drug has been known for many years.

Studies published in scientific literature show its effectiveness as a modulator/normaliser of capillaries in particular pathological conditions (see references 1, 2 and 3).
More recent studies have revealed that aminaphtone is also effective against disorders related to an endothelial damage of the arteriovenous microcirculation. Aminaphtone in fact inhibits the synthesis of endogenous substances responsible for the endothelial damage such as E-selectin, and endothelin-1, thereby highlighting its essential role in the prevention and treatment of various inflammatory diseases of the microcirculation (see references 4 and 5).
In addition, as regards pulmonary hypertension, experimentally induced in rats by the administration of monocrotaline, the effectiveness of aminaphtone was highlighted concerning various parameters investigated, such as the reduction of the plasma concentration of endothelin and of the hypertrophy of the right heart and the reduction in thickness of the pulmonary arteries (see reference 6).
The synthesis of aminaphtone was first described in U.S. Pat. No. 3,639,432.
The last two steps of the multi-step synthesis provides firstly the formation of an ester bond between 2-hydroxy-3-methyl-1,4-naphthohydroquinone and one p-nitrobenzoyl halide in benzene, and subsequently the catalytic hydrogenation in dioxane under pressure, to obtain the final product. This preparation is shown in Scheme 1 below.

The use of toxic solvents and drastic conditions make this preparation method poorly suitable for an industrial scale. Furthermore, the aminaphtone obtained through this process, has a degree of purity that is unsuitable for use as a drug. In fact, an impurity rapidly forms alongside the aminaphtone, that corresponds to an over-oxidation product with the following formula:

Recently a new method for the synthesis of aminaphtone was described in the European patent application EP2390246A1.
The above European patent application discloses that it is possible to obtain the aminaphtone with high purity by reaction of 2-hydroxy-3-methyl-1,4-naphthohydroquinone and p-nitrobenzoyl chloride in toluene, and subsequent catalytic hydrogenation in dioxolane under reduced pressure, in the presence of a metal catalyst.
This synthesis despite being more advantageous than U.S. Pat. No. 3,639,432, continues to make use of toxic substances such as pyridine; traces of palladium on carbon may also be present in the production batches, thus preventing its use in the pharmaceutical field.
Therefore, there is still the need to develop a new process for the synthesis of aminaphtone that does not make use of toxic substances, and makes it possible to obtain a final product with a high degree of purity, without having to resort to numerous purification steps.